Endocrinology, Vol 117, 565-570, Copyright © 1985 by Endocrine Society
Thyrotropin-releasing hormone metabolism and extraction by the perfused guinea pig placenta
T Nogimori, S Alex, S Baker and CH Emerson
This report describes the extraction of synthetic TRH and its metabolic
conversion in the perfused guinea pig placenta. These studies were
performed to obtain an estimate of fractional fetal TRH losses through the
placenta and to determine if some of these losses are due to TRH
metabolism. The in situ guinea pig placenta was perfused through an
umbilical artery for 90 min, and placental effluent fractions were
collected at timed intervals from the umbilical vein. Experiments were
performed in which the perfusion buffer contained 0.01, 1, and 10
micrograms/ml or no synthetic TRH. Synthetic TRH was always perfused in the
presence of 3H2O. In experiments in which TRH was perfused, the perfusion
reservoir contents and placental effluent fractions were counted for 3H,
and TRH and deamido-TRH were determined by RIA. Similarly, cyclo(His-Pro)
was measured when 10 micrograms/ml TRH were perfused. When no TRH was
perfused, the perfusion reservoir and placental effluent contents were
processed to determine their content of TRH immunoreactivity. When
synthetic TRH was perfused, steady state TRH concentrations were achieved
in placental effluent fractions by 20- 30 min. The single pass extraction
of TRH by the placenta was 11.4 +/- 2.6% (mean +/- SE) compared to 56.9 +/-
7.0% for 3H2O (P less than 0.001). No significant difference was detected
regardless of whether 10, 1, or 0.01 micrograms/ml TRH were perfused. A
portion of the TRH that perfused the placenta was converted to deamido-TRH
at all concentrations of perfused TRH. No conversion of TRH to
cyclo(His-Pro) was noted when the highest concentration (10 micrograms/ml)
of TRH was perfused. The conversion of TRH to TRH-OH was 4.2 +/- 0.7% in a
single pass. When the perfusion buffer was devoid of synthetic TRH, a small
but significant increase in the content of TRH immunoreactivity was noted
in the placental effluent compared to that in the perfusion reservoir. This
was not large enough to affect calculations of the placental extraction of
TRH. These studies, in addition to demonstrating that the placenta contains
TRH deamidase activity, suggest that losses of fetal TRH through the
placenta are not large. They do not support the current impression, based
on the fetal TSH response to maternal TSH administration, that the placenta
is freely permeable to TRH.
